Meltonin (MT) is secreted by the pineal gland (PG) almost exclusively at night. Our pevious work has shown that MT is present in humans and that its secretion can be suppressed with bright artificial light (greater than 2000 lux). This effect of light is presumed to be mediated by neural pathways connecting the retina to the PG via the hypothalamus. At the hypothalamic level the effect of light is thought to be mediated by nicotinic cholinergic receptors. Suppression of MT is presently the only index of hypothalamic sensitivity to light. We have shown that humans have a high threshold for light-MT effects compared with experimental animals. Ordinary artificial light, for example, is ineffective in humans. Abnormal hypothalamic sensitivity to light may be an important trait and pathogenic mechanism in manic-depressive illness, seasonal affective disorder and delayed sleep phase syndrome. The purpose of this project is (1) to standardize the light-MT suppression test (LMST), (2) to identify sources of variance in the LMST (age, sex, prior sleep or waking, and prior exposure to light), and (3) to investigate hypothlamic sensitivity to light using the LMST in the disorders outlined above. We will standardize the administration of light by using a xenon light source, infrared and ultraviolet filters, fiberoptic light guides, and ganzfeld-type goggles. Intensities of light can be varied using neural density filters. If desired, monochromatic filters can also be used. Light will be administered for one hour. Blood samples will be obtained before and at the end of light adminstration. Using these methods we will develop a fluence-response curve for the LMST in which degree of MT suppression is expressed as a function of log light intensity (watts/square cm).